Differential Involvement of Orbital Fat and Extraocular Muscles in Graves' Ophthalmopathy

Graves' ophthalmopathy (GO) is characterized by swelling of orbital fat and extraocular muscles, but little attention has been given to differential involvement of fat and muscles. Advancements in imaging allow rather accurate measurements of orbital bony cavity volume (OV), fat volume (FV) and muscle volume (MV), and are the topics of this review. Ratios of FV/OV and MV/OV neutralize gender differences. In adult Caucasian controls, mean values ± SD of FV/OV are 0.56 ± 0.11 and of MV/OV are 0.15 ± 0.02. FV increases substantially and MV decreases slightly with advancing age, requiring age-specific reference ranges. In 95 consecutive untreated Caucasian GO patients, both FV and MV were within normal limits in 25%, increased FV but normal MV was present in 5%, normal FV but increased MV was detected in 61%, and both increased FV and MV was evident in 9%. Increased FV was associated with more proptosis and longer GO duration. Increased MV was associated with older age, more severe GO (more proptosis and diplopia, worse eye muscle ductions), higher TBII and current smoking. At the cellular and molecular level differential involvement of fat and muscles might be related to differences between fibroblast phenotypes and cytokine profiles in each compartment, to different orbital T cell subsets during the course of the disease and to peroxisome proliferator activator receptor-γ polymorphisms and modulation of 11β-hydroxysteroid dehydrogenase-1. Enlarged muscles are apparently a rather early phenomenon in GO, whereas increases in fat mass occur relatively late. Why a minor subset of GO patients presents with an increase of only fat remains poorly understood.